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Gene Review

SQLE  -  squalene epoxidase

Homo sapiens

Synonyms: ERG1, SE, Squalene epoxidase, Squalene monooxygenase
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Disease relevance of SQLE

  • The cDNA for human squalene monooxygenase, a key enzyme in the committed pathway for cholesterol biosynthesis, was amplified from a human liver cDNA library and cloned, and the protein was expressed in Escherichia coli and purified [1].
  • Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome [2].
  • From these observations, squalene epoxidase inhibitor is expected to be highly effective in the treatment of hypercholesterolemia and also is very useful as a research tool for studying the regulation of cholesterol metabolism [3].
  • We propose that an increase in cardiac calcium current and reduced trafficking of hERG channels to the cell surface cause QT prolongation and torsade de pointes in patients treated with As(2)O(3) [4].
  • The human ether-a-go-go related gene (hERG) can be inhibited by marketed drugs, and this inhibition may lead to QT prolongation and possibly fatal cardiac arrhythmia [5].

Psychiatry related information on SQLE

  • The main factors studied are context characteristics and constructs of attitude, social influence, self-efficacy (SE) and perceived barriers [6].
  • OBJECTIVES: Study aim was to adapt a Dutch/English version of the diabetes management self-efficacy (SE) scale for use with a Turkish population and evaluate its psychometric properties [7].
  • This study aimed at exploring the existing predominant critical thinking disposition(s) of baccalaureate nursing students and the relationship among their critical thinking (CT), self-esteem (SE), and state anxiety (SA) [8].

High impact information on SQLE

  • Maximal amounts of 12-HETE were 126 +/- 21 pmol/10(6) cells (+/- SE), and concentration-response curves yielded half-maximal levels for 12-HETE similar to PGE2 at 2 microM AA [9].
  • Two enzymes, squalene monooxygenase and oxidosqualene cyclase, are the minimum necessary for initial biosynthesis of sterols from squalene [10].
  • In this work, 19 protein gene sequences for eukaryotic squalene monooxygenase and 12 protein gene sequences for eukaryotic oxidosqualene cyclase were compared with all available complete and partial prokaryotic genomes [10].
  • We found that 1a and 1b N-terminal fragments bind in a direct and dose-dependent manner. hERG1 hetero-oligomerization occurs in the endoplasmic reticulum where co-expression of N-terminal fragments with hERG1 subunits disrupted oligomerization and core glycosylation [11].
  • Alternate transcripts of the human ether-à-go-go-related gene (hERG1) encode two subunits, hERG 1a and 1b, which form potassium channels regulating cardiac repolarization, neuronal firing frequency, and neoplastic cell growth [11].

Chemical compound and disease context of SQLE


Biological context of SQLE


Anatomical context of SQLE


Associations of SQLE with chemical compounds

  • The increase of SE mRNA in HeLa cells grown in LPDS was preventable in a dose-dependent manner by feeding cells with 25-hydroxycholesterol or cholesterol [17].
  • These results suggest that sterol produced endogenously can also regulate SE expression at the level of transcription [17].
  • Overexpression/selection using the sterol synthesis inhibitors terbinafine (TBF, targeting squalene epoxidase) and itraconazole (ITZ, targeting lanosterol C(14)-demethylase) yielded nine new resistance loci [21].
  • NB-598: a potent competitive inhibitor of squalene epoxidase [22].
  • Grapefruit juice increased the mean felodipine area under the plasma concentration-time curve (AUC) (mean +/- SE, 55 +/- 9 nmol. h/L versus 29 +/- 6 nmol. h/L; P <.05) and the plasma peak drug concentration (16 +/- 3 nmol/L versus 8 +/- 2 nmol/L, P <.05) and decreased the dehydrofelodipine/felodipine AUC ratio compared with those of water [23].

Regulatory relationships of SQLE

  • We found that decreasing OSBP expression by approximately 90% did not affect 25-HC-induced inhibition of transcription of 3-hydoxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and squalene epoxidase to any extent [24].

Other interactions of SQLE


Analytical, diagnostic and therapeutic context of SQLE

  • To refine the localization of human SQLE further, PCR on the Stanford G3 Radiation Hybrid Panel was performed [16].
  • Moreover, fluorescence in situ hybridization also maps human SQLE to 8q24.1 [16].
  • An increased expression of SE mRNA and protein content in mouse L929 cells grown in 10% lipoprotein-deficient fetal bovine serum (LPDS) for 48 h was found by performing immunoblot and Northern blot analyses when compared with the culture in the presence of fetal bovine serum (FBS) [17].
  • Here, RT-PCR was used to monitor the circadian expression of ether-a-go-go-related gene (Erg) potassium channel isoforms and Erg1 splice variants [27].
  • Comparative molecular field analysis (CoMFA) of fungal squalene epoxidase inhibitors exhibiting antifungal activity reported in terms of minimum inhibitory concentration (MIC) was performed [28].


  1. Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase. Laden, B.P., Tang, Y., Porter, T.D. Arch. Biochem. Biophys. (2000) [Pubmed]
  2. Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome. Gong, Q., Jones, M.A., Zhou, Z. J. Biol. Chem. (2006) [Pubmed]
  3. Effect of a novel squalene epoxidase inhibitor, NB-598, on the regulation of cholesterol metabolism in Hep G2 cells. Hidaka, Y., Hotta, H., Nagata, Y., Iwasawa, Y., Horie, M., Kamei, T. J. Biol. Chem. (1991) [Pubmed]
  4. Mechanisms of arsenic-induced prolongation of cardiac repolarization. Ficker, E., Kuryshev, Y.A., Dennis, A.T., Obejero-Paz, C., Wang, L., Hawryluk, P., Wible, B.A., Brown, A.M. Mol. Pharmacol. (2004) [Pubmed]
  5. Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniques. Ekins, S., Balakin, K.V., Savchuk, N., Ivanenkov, Y. J. Med. Chem. (2006) [Pubmed]
  6. Focus points for school health promotion improvements in Dutch primary schools. Leurs, M.T., Bessems, K., Schaalma, H.P., de Vries, H. Health education research (2007) [Pubmed]
  7. Cross-cultural adaptation of the Diabetes Management Self-Efficacy Scale for patients with type 2 diabetes mellitus: scale development. Kara, M., van der Bijl, J.J., Shortridge-Baggett, L.M., Asti, T., Erguney, S. International journal of nursing studies. (2006) [Pubmed]
  8. Critical thinking, self-esteem, and state anxiety of nursing students. Suliman, W.A., Halabi, J. Nurse education today (2007) [Pubmed]
  9. A regiospecific monooxygenase with novel stereopreference is the major pathway for arachidonic acid oxygenation in isolated epidermal cells. Holtzman, M.J., Turk, J., Pentland, A. J. Clin. Invest. (1989) [Pubmed]
  10. Phylogenetic and biochemical evidence for sterol synthesis in the bacterium Gemmata obscuriglobus. Pearson, A., Budin, M., Brocks, J.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  11. Heteromeric Assembly of Human Ether-a-go-go-related Gene (hERG) 1a/1b Channels Occurs Cotranslationally via N-terminal Interactions. Phartiyal, P., Jones, E.M., Robertson, G.A. J. Biol. Chem. (2007) [Pubmed]
  12. Squalene epoxidase as hypocholesterolemic drug target revisited. Chugh, A., Ray, A., Gupta, J.B. Prog. Lipid Res. (2003) [Pubmed]
  13. Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls. Laden, B.P., Porter, T.D. J. Lipid Res. (2001) [Pubmed]
  14. Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine: a case-study in cardiac safety pharmacology. Hancox, J.C., Mitcheson, J.S. Br. J. Pharmacol. (2006) [Pubmed]
  15. Refinement of Catalyst hypotheses using simplex optimisation. Norinder, U. J. Comput. Aided Mol. Des. (2000) [Pubmed]
  16. Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1. Nagai, M., Sakakibara, J., Wakui, K., Fukushima, Y., Igarashi, S., Tsuji, S., Arakawa, M., Ono, T. Genomics (1997) [Pubmed]
  17. Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells. Nakamura, Y., Sakakibara, J., Izumi, T., Shibata, A., Ono, T. J. Biol. Chem. (1996) [Pubmed]
  18. SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase. Nagai, M., Sakakibara, J., Nakamura, Y., Gejyo, F., Ono, T. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  19. Role of supernatant protein factor and anionic phospholipid in squalene uptake and conversion by microsomes. Chin, J., Bloch, K. J. Biol. Chem. (1984) [Pubmed]
  20. Regulation of squalene epoxidase in HepG2 cells. Hidaka, Y., Satoh, T., Kamei, T. J. Lipid Res. (1990) [Pubmed]
  21. Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection. Cotrim, P.C., Garrity, L.K., Beverley, S.M. J. Biol. Chem. (1999) [Pubmed]
  22. NB-598: a potent competitive inhibitor of squalene epoxidase. Horie, M., Tsuchiya, Y., Hayashi, M., Iida, Y., Iwasawa, Y., Nagata, Y., Sawasaki, Y., Fukuzumi, H., Kitani, K., Kamei, T. J. Biol. Chem. (1990) [Pubmed]
  23. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice. Bailey, D.G., Dresser, G.K., Bend, J.R. Clin. Pharmacol. Ther. (2003) [Pubmed]
  24. Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of OSBP. Nishimura, T., Inoue, T., Shibata, N., Sekine, A., Takabe, W., Noguchi, N., Arai, H. Genes Cells (2005) [Pubmed]
  25. Toxins interacting with ether-à-go-go-related gene voltage-dependent potassium channels. Wanke, E., Restano-Cassulini, R. Toxicon (2007) [Pubmed]
  26. Modification of the nucleotide cofactor-binding site of cytochrome P-450 reductase to enhance turnover with NADH in Vivo. Elmore, C.L., Porter, T.D. J. Biol. Chem. (2002) [Pubmed]
  27. Circadian changes of ether-a-go-go-related-gene (Erg) potassium channel transcripts in the rat pancreas and beta-cell. Mühlbauer, E., Bazwinsky, I., Wolgast, S., Klemenz, A., Peschke, E. Cell. Mol. Life Sci. (2007) [Pubmed]
  28. Comparative molecular field analysis of fungal squalene epoxidase inhibitors. Gokhale, V.M., Kulkarni, V.M. J. Med. Chem. (1999) [Pubmed]
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